This invention concerns novel compounds that act as selective inhibitors for Chk2. The compounds possess the cellular activity to regulate the Chk2-mediated cell cycle arrest and apoptosis. They are potentially useful as radiation protection agents in anticancer radiotherapy.
The maintenance of an intact genome is of crucial importance to every organism. Each individual cell in a multicellular eukaryotic organism possesses sophisticated and intricate mechanisms to properly respond to DNA damage. Such mechanisms repair damaged DNA or trigger programmed cell death (apoptosis). Checkpoint kinases are thought to be intimately involved in these processes.
Checkpoint Kinase 2 (“Chk2”) is one of the major effectors of the replication checkpoint. The crucial roles played by Chk2 in mediating cellular responses to DNA damage implicate its potential value in cancer therapies. The inhibition of Chk2 could protect normal cells from the effects of ionizing radiation or DNA-damaging chemotherapeutics while increasing the cancer cells' susceptibility to such treatments, thus enhancing both the efficacy and the safety of such therapies.